During the second year of study, we concentrated our efforts on examining the role of bone marrow in the leukemogenic progression which manifests in AKR mice. Marrow is the richest source of ecotropic virus infectious cell centers (ICC) which constitute approximately 1% of the total bone marrow cell population. Our findings indicate that marrow ICC express high levels of both viral envelope glycoprotein (gp71) and Class I histocompatibility antigens (H-2K[unreadable]k[unreadable]). Marrow ICC appear to be devoid of Class II histocompatibility antigens as well as Thy 1.1 and asialo-GM-1 antigens. In addition, they are contained in both phagocytic and non-phagocytic fractions of cells as well as plastic adherent and non-adherent populations. Marrow ICC were enriched 5 to 10 fold at the lymphoid interface of Ficoll-Hypaque. Likewise, ICC were significantly enriched in the adherent fraction of nylon wool separated bone marrow. Nylon wool adherent cells similarly displayed increased Class I antigen expression. Discontinuous Percoll fractionation yielded two fractions of cells comprising approximately 15% of total marrow cells and 85% of total ICC. These cells exhibited a low density and morphologically appeared to be large blast and granulocytic cells. Although ICC were significantly enriched in these two fractions, viral gp71 expression was nearly constant in all fractions--including those devoid of ICC. This suggests that virus expression occurs in immature hematopoietic cells and that maturation may turn off virus production but not gene expression. We have attempted to duplicate the therapeutic effects of polyclonal IgG with specific monoclonal antibodies and have found that one particular monoclonal suppresses the neonatal burst of ICC in a manner analogous to our polyclonal reagents. Lastly, we have found that combined anti-gp71 and anti-p15E therapy can suppress leukemogenesis even when administered outside of the "therapy window'. (IT)